EP0979652B1 - Composition curative de l'hypertension intraoculaire ou du glaucome - Google Patents

Composition curative de l'hypertension intraoculaire ou du glaucome Download PDF

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Publication number
EP0979652B1
EP0979652B1 EP98945530A EP98945530A EP0979652B1 EP 0979652 B1 EP0979652 B1 EP 0979652B1 EP 98945530 A EP98945530 A EP 98945530A EP 98945530 A EP98945530 A EP 98945530A EP 0979652 B1 EP0979652 B1 EP 0979652B1
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EP
European Patent Office
Prior art keywords
latanoprost
composition
isopropyl unoprostone
glaucoma
present
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP98945530A
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German (de)
English (en)
Other versions
EP0979652A1 (fr
EP0979652A4 (fr
Inventor
Ryuji Ueno
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
R Tech Ueno Ltd
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R Tech Ueno Ltd
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Publication date
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Publication of EP0979652A4 publication Critical patent/EP0979652A4/fr
Application granted granted Critical
Publication of EP0979652B1 publication Critical patent/EP0979652B1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics

Definitions

  • the Present invention provides a composition for treatment of ocular hypertension or glaucoma.
  • the invention provides a composition, which can enhance the effect of known compounds synergistically and can reduce the occurrence of unfavorable side effects.
  • Isopropyl unoprostone (common name), a compound which is used as a component (a) of the present invention, is (+)-isopropyl-Z-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl] hept-5-enoate.
  • An ocular hypotensive activity of this compound was described in EP-A-0308135 (corresponds to JP-A-02-108).
  • Latanoprost (common name), a compound which is used as a component (b) of the present invention, is (+)-isopropyl-Z-7- ⁇ (1R, 2R, 3R, 5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl] cyclopentyl ⁇ -5-heptenoate.
  • An ocular hypotensive activity of this compound was described in EP-A-0364417 (corresponds to JP-A-03-501025).
  • any prior art does not teach the combined administration of the components (a) and (b) of the present invention, the effect may be increased synergistically, nor the adverse side effect may be reduced by the combination.
  • An object of the present invention is to provide a composition for treatment of ocular hypertension or glaucoma, especially a composition which can provide a synergistic effect and reduce adverse side-effects.
  • the present invention provides a composition useful for treatment of ocular hypertension or glaucoma comprising; (a) isopropyl unoprostone, and (b) Latanoprost.
  • Isopropyl unoprostone (common name), the compound used for component (a), is (+)-isopropyl-Z-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl] hept-5-enoate.
  • This compound has an ocular hypotensive activity, and different from natural PGs, does not induce transient increase of intraocular pressure. Therefore, the composition of the present invention may be applied for treatment of various diseases and conditions in which reduction of intraocular pressure is desired, for example, glaucoma, ocular hypertension and the other diseases accompanied by increased intraocular pressure.
  • treatment or treating in this specification and claims refers to any means of control, including preventing or curing the disease, relieving or alleviating the condition, and arresting the development of the condition.
  • Latanoprost (common name), the compound used for component (b) in the present invention, is (+)-isopropyl-Z-7- ⁇ (1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl] cyclopentyl ⁇ -5-heptenoate.
  • This compound has been known to have an ocular hypotensive activity, and also to have some adverse side effects such as transient increase of intraocular pressure, hyperemia of conjunctiva, ocular irritation, and iris pigmentation.
  • the combined administration of the component (a) and (b) provides a synergistic effect. That is, since the combination enhances the desired effects of each of the components (a) and (b) synergistically, the dose of the each component can be reduced, and therefore, adverse side effects of the each component can be effectively reduced.
  • the ratio of (a): (b) is not limited but in general about 1:0.005-1:2, preferably, about 1:0.01-1.
  • each component in the present composition may vary depending on state of the patient to be treated, severity of the condition, object of the treatment, diagnosis by a doctor, and total amount of administration.
  • the amount of the component (a) in the composition is about 0.005-2 wt%, preferably, 0.01-1 wt%.
  • the amount of the component (b) in the composition is about 0.0001-2 wt%, preferably, 0.0005-1 wt%.
  • the components (a) and (b) may be administered either simultaneously or individually.
  • composition of the present invention may be formulated to contain both of the components (a) and (b) in a single dosage unit, or may be a package consisting of separate dosage units containing each component respectively.
  • the composition of the present invention may further contain any conventional compound used in ophthalmologic composition such as carrier and adjuvant.
  • composition of the present invention may be formulated as liquids such as solution, emulsion, and suspension, or as semisolids such as gel or ophthalmic ointment.
  • diluent for an aqueous solution or suspension examples include distilled water and physiological saline.
  • diluent for a non-aqueous solution or suspension include vegetable oil, liquid paraffin, mineral oil, propylene glycol and p-octyldodecanol and the like.
  • isotonic agents such as sodium chloride, boric acid and sodium citrate to make isotonic with the lacrimal fluid
  • buffering agents such as borate buffer and phosphate buffer to maintain pH about 5.0 to 8.0 may be contained in the present composition.
  • stabilizing agents such as sodium sulfite and propylene glycol, chelating agents such as sodium edetate, thickening agents such as glycerin, carboxymethyl cellulose and carboxyvinyl polymer, and preservatives such as methyl paraben, propyl paraben may be contained in the composition.
  • the ingredients are sterilized by means of, for example, passing through a bacterial filter or heating.
  • the ophthalmic ointment may contain, such as, vaseline, Zelen 50, Plastibase and Macrogol as base components and a surfactant for increasing hydrophilicity. Further, the composition may contain gelling agents such as carboxymethylcellulose, methylcellulose, carboxyvinyl polymer, as well.
  • composition of the present invention may contain antibiotics such as chloramphenicol and penicillin, for preventing or treating bacterial infection.
  • the present invention further provides the use of (a) isopropyl unoprostone and (b) Latanoprost for manufacturing a pharmaceutical composition for treatment of ocular hypertension or glaucoma.
  • Latanoprost eye drops were administrated at 22 o'clock and then isopropyl unoprostone eye drops were administrated at 10 o'clock in the next morning, that is 12 hours after Latanoprost administration.
  • the monkeys were anesthetized intramuscularly with 5.0-7.5 mg/kg of Ketamin (Sankyo Pharmaceuticals Co. Ltd.). A time course of the intraocular pressure was determined under topical anesthetization by dropping 0.4 % oxybuprocaine hydrochloride (Santen Pharmaceutical Co Ltd.) to eyes, by means of applanation pneumatonograph (Nippon Alcon).
  • the present invention is useful for treatment of ocular hypertension or glaucoma.

Claims (6)

  1. Composition pour le traitement de l'hypertension oculaire ou du glaucome, comprenant (a) de l'isopropyle d'unoprostone et (b) du atanoprost.
  2. Composition selon la revendication 1, dans laquelle lesdits (a) isopropyle d'unoprostone et (b) atanoprost sont contenus dans une seule dose unitaire.
  3. Composition selon la revendication 1, dans laquelle lesdits (a) isopropyle d'unoprostone et (b) atanoprost sont respectivement contenus dans des doses unitaires distinctes.
  4. Utilisation de (a) isopropyle d'unoprostone et (b) atanoprost pour la fabrication d'une composition pharmaceutique pour le traitement de l'hypertension oculaire ou du glaucome.
  5. Utilisation selon la revendication 4, dans laquelle ladite composition pharmaceutique contient (a) de l'isopropyle d'unoprostone et (b) du atanoprost sous la forme d'une seule dose unitaire.
  6. Utilisation selon la revendication 4, dans laquelle ladite composition pharmaceutique contient (a) de l'isopropyle d'unoprostone et (b) du atanoprost sous la forme, respectivement, de doses unitaires distinctes.
EP98945530A 1997-10-13 1998-09-30 Composition curative de l'hypertension intraoculaire ou du glaucome Expired - Lifetime EP0979652B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP27854097 1997-10-13
JP27854097 1997-10-13
PCT/JP1998/004399 WO1999018969A1 (fr) 1997-10-13 1998-09-30 Composition curative de l'hypertension intraoculaire ou du glaucome

Publications (3)

Publication Number Publication Date
EP0979652A1 EP0979652A1 (fr) 2000-02-16
EP0979652A4 EP0979652A4 (fr) 2003-05-14
EP0979652B1 true EP0979652B1 (fr) 2006-05-24

Family

ID=17598695

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98945530A Expired - Lifetime EP0979652B1 (fr) 1997-10-13 1998-09-30 Composition curative de l'hypertension intraoculaire ou du glaucome

Country Status (9)

Country Link
US (1) US6329426B1 (fr)
EP (1) EP0979652B1 (fr)
AT (1) ATE326972T1 (fr)
CA (1) CA2274708A1 (fr)
DE (1) DE69834638T2 (fr)
DK (1) DK0979652T3 (fr)
ES (1) ES2265166T3 (fr)
HK (1) HK1024170A1 (fr)
WO (1) WO1999018969A1 (fr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5011548B2 (ja) * 1998-12-25 2012-08-29 株式会社アールテック・ウエノ 高眼圧症あるいは緑内障の処置用医薬組成物
WO2002060387A2 (fr) * 2001-01-30 2002-08-08 Pharmaceutical Research Corporation Utilisation d'analogues de prostaglandine dans le traitement d'etats cardiaques
DE60326226D1 (de) * 2002-03-21 2009-04-02 Cayman Chemical Co Prostaglandin f2 alpha analoga in kombination mit einem antimikrobiellen mittel zur behandlung von glaukom
WO2003082257A2 (fr) * 2002-03-28 2003-10-09 Sucampo Ag Methode de traitement de l'hypertension oculaire et du glaucome
US20020168424A1 (en) * 2002-07-31 2002-11-14 Dr. Mohsen Shahinpoor Nitric oxide (NO) donor+cGMP-PDE5 inhibitor as a topical drug for glaucoma
US6864282B2 (en) 2002-08-05 2005-03-08 Allergan, Inc. 9,11-cycloendoperoxide pro-drugs of prostaglandin analogues for treatment of ocular hypertension and glaucoma
AR043161A1 (es) * 2003-02-14 2005-07-20 Sucampo Pharmaceuticals Inc Composicion oftalmica para tratar hipertension ocular y glaucoma
US7320871B2 (en) * 2003-07-14 2008-01-22 Allergan, Inc. Human prostaglandin FP receptor variants and methods of using same
CN103768070A (zh) * 2006-03-13 2014-05-07 株式会社·R-技术上野 水性组合物
WO2008120249A1 (fr) * 2007-03-30 2008-10-09 Sifi S.P.A. Produits pharmaceutiques à base de lipides polaires et non polaires pour utilisation ophtalmique
EP2127638A1 (fr) * 2008-05-30 2009-12-02 Santen Pharmaceutical Co., Ltd Procédé et composition pour traiter l'hypertension oculaire et le glaucome
WO2017089980A1 (fr) * 2015-11-26 2017-06-01 Cadila Healthcare Limited Doubles modulateurs de ppar pour le traitement de la rétinopathie diabétique et des maladies oculaires liées au diabète

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0308135B1 (fr) 1987-09-18 1992-11-19 R-Tech Ueno Ltd. Agents hypotenseurs ophtalmologiques
ES2186670T3 (es) * 1988-09-06 2003-05-16 Pharmacia Ab Derivados de prostaglandina para el tratamiento del glaucoma o la hipertension ocular.
GB8916944D0 (en) 1989-07-25 1989-09-13 Ici Plc Composite particle dispersions
DE69232150T2 (de) * 1992-03-19 2002-03-07 R Tech Ueno Ltd Behandlung von Augenhochdruck mit Betablockern und Prostansäurederivaten
AU665287B2 (en) * 1992-12-21 1995-12-21 Alcon Laboratories, Inc. Prostaglandin combinations in glaucoma therapy
WO1997023225A1 (fr) * 1995-12-22 1997-07-03 Alcon Laboratories, Inc. Combinaisons de prostaglandines de type dp et fp destinees a abaisser la pression intraoculaire

Also Published As

Publication number Publication date
DE69834638T2 (de) 2007-05-10
EP0979652A1 (fr) 2000-02-16
ATE326972T1 (de) 2006-06-15
CA2274708A1 (fr) 1999-04-22
EP0979652A4 (fr) 2003-05-14
WO1999018969A1 (fr) 1999-04-22
DK0979652T3 (da) 2006-09-11
DE69834638D1 (de) 2006-06-29
US6329426B1 (en) 2001-12-11
ES2265166T3 (es) 2007-02-01
HK1024170A1 (en) 2000-10-05

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